Innate Immune Cells Have Some Memory

A new study of an oft-neglected arm of the immune system may cause researchers to rethink how it helps defend the body from infection.

The body’s immune system has 2 parts: one responsible for “innate” immunity and the other for “adaptive” immunity. Rapid and blunt, the innate immune system is the first line of defense. It recognizes a limited number of molecular patterns in disease-causing microbes, or pathogens. Convention says that the innate immune system retains no memory of previous infections.

The adaptive immune system, in contrast, produces antibodies and cells that recognize highly specific parts of pathogens. It can match a limitless repertoire of molecules, enabling it to adapt to virtually any pathogen that enters the body. It also retains a memory, so that if you ever encounter a pathogen again, the system quickly mounts a response and fights it off much faster than it did the first time.

Much research has focused on adaptive immunity because of its role in vaccinations. Vaccines work by causing the adaptive immune system to "remember" molecules from infectious agents before the real pathogens ever enter your body.

A research team led by Dr. Megan Cooper in Dr. Wayne M. Yokoyama's laboratory at Washington University School of Medicine saw hints in the literature that the innate immune system may not be as limited as it seems. They decided to investigate, with support from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), along with the Howard Hughes Medical Institute.

The researchers focused on natural killer (NK) cells, innate immune cells with a limited repertoire of receptors to recognize their targets. NK cells also produce interferon gamma to signal other immune cells. NK cells are technically challenging to study because they don't live long outside the body. The researchers isolated NK cells from mouse spleens and cultured them overnight in solution. Some were given hormone-like molecules called cytokines to activate them, while control cells were left unactivated. The cells were then labeled with a cell-tracking dye. Mice were given either the activated or control cells intravenously.

In the January 30, 2009, online edition of the Proceedings of the National Academy of Sciences, the scientists reported that labeled NK cells were easily detected 1 to 3 weeks later in mouse spleens. The previously activated NK cells didn't spontaneously produce more interferon gamma than control NK cells. However, when isolated cells were activated in the lab, the previously activated NK cells produced significantly more interferon gamma than the control cells.

There was no difference in cell killing activity between the control and previously activated cells. The difference seems to be that the cells retained a memory of their prior activation—a function until now attributed only to adaptive immune cells.

"Natural killer cells have limited abilities to recognize a particular pathogen, but we found that once they've been activated by cytokines, they can respond more easily and effectively to the next call for activation," Yokoyama says. "It should be possible to therapeutically exploit these memory-like properties to make more effective immune cells."